The present invention relates to an article for dispensing small volumes of liquid.
Pharmaceutical screening of drug candidates, clinical research and applications, genetic research, combinatorial chemistry, analysis and printing, among others, depend on accurate dispensing of very small volumes of liquid. Carrying out methods in such fields using very small volumes of liquid, as opposed to larger volumes, facilitates rapid screening operations, decreases reagent usage and decreases disposal requirements. It is, however, rather difficult to accurately and reliably dispense such small volumes of liquid.
Dispensing liquid volumes within a range of tens of nanoliters to about 2 microliters is particularly problematic. The difficulty lies in overcoming the surface tension between the dispensable liquid and the dispenser. Specifically, the weight of such a small volume of liquid is insufficient to overcome surface tension effects. This difficulty affects the accuracy and repeatability of the dispensing operation.
One method for nano- and micro-volume dispensing is to xe2x80x9cpushxe2x80x9d a small portion of the dispensable liquid out of its dispenser and bring the exposed liquid into contact with a receiver. This method, referred to as xe2x80x9ctouch-offxe2x80x9d transfer, utilizes the surface tension between the exposed liquid and the receiver (or liquid in the receiver) to draw the desired volume of dispensable liquid out of its dispenser. Exemplary touch-off dispensers include capillary tubes, wettable pegs or pins and syringes.
While mechanically simple and inexpensive, touch-off transfer is a relatively slow process. Furthermore, the repeatability and accuracy of touch-off transfer is suspect. In addition, touch-off dispensers may cause undesirable carry-over or cross contamination wherein a substance within the receiver is drawn into or onto the dispenser. To avoid contamination, touchoff dispensers must be cleaned between dispensing cycles, and, in fact, complete replacement of dispensing tips may be required. Moreover, touch-off transfer cannot always be used as it depends on surface and liquid parameters.
In a second method for nano- and micro-volume dispensing, dispensable liquid is forcibly ejected from a dispenser, thereby overcoming surface tension. This method is referred to as xe2x80x9cnon touch-offxe2x80x9d transfer. Exemplary non touch-off dispensers include flow modulators, micrometering pumps and piezo- or thermally-activated liquid ejectors as are often used in print heads. While avoiding some of the problems that plague touch-off dispensers, non touch-off dispensers have other drawbacks. In particular, liquid ejectors are usually restricted to use with a very limited range of volumes and typically require very clean and specially developed fluids. Pumps and flow modulators tend to be slow, have limited reliability and are often incompatible with biochemical or chemical reagents.
As such, there is a need for a dispenser that is capable of dispensing nano- and microvolumes of liquid and that avoids the drawbacks of prior art touch-off and non touch-off dispensers.
A method and article for dispensing very small volumes of liquid is disclosed. The present dispenser uses non touch-off transfer thereby avoiding the possibility of cross contamination. Yet, it is implemented in a manner that avoids the above-discussed limitations of most prior-art non touch-off dispensers.
In accordance with the present teachings, some embodiments of the present article utilize centrifugal forces to eject liquid volumes in the range of tens of nanoliters to several microliters from a dispensing element. In one embodiment, the present dispenser comprises a rotating element (hereinafter xe2x80x9crotatorxe2x80x9d) that develops and maintains a predetermined speed of rotation. The rotator rotates a rotatable element (hereinafter xe2x80x9crotorxe2x80x9d). The rotor contains (1) a dispensing system and (2) a carrier that supports a plurality of liquid receivers.
The dispensing system includes one or more dispensing elements and a device(s) for delivering a desired quantity of liquid to each dispensing element. For example, in one embodiment, the dispensing system comprises a multiplicity of syringe pumps operatively connected to a like number of dispensing needles. Each syringe pump advances a desired volume of liquid from its reservoir to the tip of the communicating needle for dispensing. The volume of liquid is dispensed due to the centrifugal force generated by the rotator. The liquid is dispensed toward a liquid receiver that is disposed near to and facing the syringes.
The carrier that supports the liquid receivers is advantageously advanceable in a predetermined step with reference to the dispensing element (e.g., the needles). This feature allows liquid to be dispensed into each one of a plurality of liquid receivers that are disposed on the carrier. Moreover, in some embodiments, the dispensing elements are movable in a direction perpendicular to the rotating plane and parallel to the axis of rotation in order to align, as required, with each liquid receiver.